Hundreds of genetic regions have been implicated in complex human traits in the past several years through the genome wide association study (GWAS) paradigm. Despite these successes, statistical analyses in most published work were based on single genetic markers. In addition, prior biological knowledge on genetic markers is rarely used. From both statistical and biological points of view, the rich information in the collected GWAS data has not been fully utilized to reveal disease etiologies. To address these critical needs, many research groups have been actively developing statistical and computational methods that can jointly analyze multiple markers, both within a region and across regions, and methods that can more effectively incorporate other sources of information on genetic markers, genes, and pathways in association analysis. The long- term goals of this application are to develop and implement novel statistical methods to identify genes affecting an individual's susceptibility to complex traits, to apply these methods to ongoing studies to enable more biological findings, and to disseminate these tools to the general research community. To achieve these broad goals, we propose to accomplish the following specific aims: (1) to develop statistical methods to identify markers that are informative about an individual's ancestry, and to take advantage of this information for more effective adjustment of sample heterogeneity in genetic association studies; (2) to develop statistical methods that can more efficiently perform multi-marker analysis, and to evaluate the statistical power of different marker search strategies; (3) to develop statistical methods that can systematically integrate different sources of information, especially biological pathways and networks, to increase our power to identify markers truly associated with complex diseases; (4) to develop statistical methods to use resequencing data to identify genetic associations between phenotypes and candidate regions. In addition, we will collaborate with leading human geneticists to apply and refine the statistical methods to a wide array of diseases, and to disseminate well-tested and validated programs to the scientific community.